Hirsutism Virilization and CAH (Darrow) - MT

Question 1

Causes of Hirsuitism which usually cause decreased sex hormone binding globulin (free testosterone) include what 9 things?

Answer 1

1. Decreased Estrogen (prolactinoma)
2. Insulin
3. GH (acromegaly)
4. Obesity
5. Hypothyroidism
6. Glucocorticiods (cushings)
7. Androgens
8. Nephrotic syndrome (protein dumping = dec SHBGs)
9. excess activity of 5-alpha-reductase

Question 2

Where is Sex hormone binding globulin (free testosterone) produced?

Answer 2

Liver (slide 3)

Question 3

This skin condition is common in what endocrine disorder?

What causes it?

Answer 3

• Hirsutism d/t CAH
• Excess circulating Androgens

Question 4

The PHODDCI pneumonic for Hirsutism stands for what causes?

Answer 4

• PCOS (LH/FSH ration >2 = decrased Est/Test)
• Hypothyroidism (dec SHBG, and inc TRH–> inc prolactin)
• Ovarian/Adrenal tumors (LH/FSH inc –> Hyperthecosis = arrested follicular developent in lutenized thecal cells–> Testosterone overproduction)
• Drugs (steroids, penicillin, minoxidil)
• Deficient 21 hydroxylase (CAH)
• Cushing syndrome (inc sec of androgens w/ cortisol)
• Idiopathic/familial (increased skin 5 alpha reductase activity)

Question 5

Ovarian causes of Hirsutism include what 2 conditions?

Answer 5

• Polycystic ovarian syndrome
• Tumors

Question 6

You recieve that labs for a patient with known hirsutism, what will you see in the testosterone, DHEAS, and 17 hydroxy progesterone levels if the cause of the patient’s hirsutism stems from:

1. Idiopathic/hereditary
2. Polycystic ovarian syndrome
3. CAH

* give mild increase, normal, or all increased anwer for the levels

Answer 6

1. Idiopathic/hereditary = All normal
2. Polycystic ovarian syndrome = testosterone mild increase
3. CAH = all increased (17 OHP> 500 ng/dL)

Question 7

Physical examination of a patient with a Virilizing condition would yield what d/t overproduction of androgens? (x5)

Answer 7

1. Increased muscularity
2. temporal alopecia
3. deepening voice
4. acne
5. clitoromegaly (adrenal, ovaries, CAH)

Question 8

Lab levels of Testosterone, DHEAS (dehydroepiandrosterone), and 17 hydroxyprogesterone in a patient suffering from virilization (not hirsutism) d/t an Ovarian tumor would be?

Answer 8

• total testosterone greatly increased

(total testosterone > 200 ng/dL points to ovary or adrenal tumor)

• normal DHEAS and 17 OHP

Question 9

Lab levels of Testosterone, DHEAS (dehydroepiandrosterone), and 17 hydroxyprogesterone in a patient suffering virilization d/t and Adrenl tumor would be?

Answer 9

• Greatly increased DHEAS > 700 ng/dL

Question 10

Lab levels of Testosterone, DHEAS (dehydroepiandrosterone), and 17 hydroxyprogesterone in a patient suffering from virilization d/t congenital adrenal hyperplasia would be?

Answer 10

• Total testosterone, DHEAS, 17OHP are all increased

(17OHP > 500 ng/dL = Diagnostic)

Question 11

Where are androgens produced?

• Increase to > 1000 ng/dL of androstenedione could indicate what?
• Increased to >700 ng/dL of DHEAS could indicate what?

Answer 11

• Adrenal gland reticularis layer
• Adrenal or Ovarian neoplasm
• Adrenal neoplasm or CAH

Question 12

1 - Total testosterone > 200 ng/dL is most indicative of what condition causing hirsutism or virilization?

2 - DHEAS >700 mcg/dL is most indicative of what condition causing hirutis or virilization?

3 - 17 OHP >500 ng/dL is diagnostic for what?

Answer 12

1 - Ovarian neoplasm

2 - Adrenal neoplasm

3 - CAH

Question 13

Treatment for histuitism includes use of antiandrogens like:

1. Spironolactone and flutamide
2. finasteride
3. Metformin
4. GnRH agonist

What are their respective general mechanisms of action?

Answer 13

1. spirnonolactone and flutamide = androgen receptor blockers
2. finasteride = 5-alpha reductase inhibitor
3. Metformin = reduces hepatic gluconeogenesis–> lowers insulin levels)
4. GnRH agonist = decreases gonadotropins by constant stimulation

Question 14

What stimulates the zona glomerulosa to produce Aldosterone?

What stimulates the zona fasciculata to produce cortisol as well as the zona reticularis to produce androstenedione?

Answer 14

• Angiotensin II, K+, ANP stim ZG
• ACTH stims ZF and ZR

Question 15

21 hydroxylase deficiency in a patient with CAH will lead to an excess of what molecule?

Answer 15

• Androgens

Question 16

What are the 2 main symptoms of 21 hydroxylase deficiency in CAH?

Why do these symptoms appear?

Answer 16

• Masculinization (virilization) in females from excess androgen (or in males more pronounced genetalia, and oligospermia)
• Hypotension salt wasting from deficient production of aldosterone)

Question 17

What is usually a diagnostic lab level of 17 OH prognenolone (androgen precursor) for CAH 21 hydroxylase deficiency? (ng/dL)

Answer 17

• > 500 ng/dL

Question 18

In 11 beta hydroxylase deficiency, a build up excess of what molecule causes masculinization and hypertension?

Answer 18

• 11 Deoxycorticosterone (DOC)

(has aldosterone like affects and can be converted into androgen pathway)

Question 19

How does the adrenal hyperplasia occur in CAH? (21 hydroxylase deficiency)

Answer 19

• lack of cortisol production eliminates negative feedback loop to hypothalamus and pituitary, thus ACTH is continuosly secreted and overstimulates the Zona fasciculata and Zona reticularis –> hyperplasia and excess androgens

Question 20

Because there is an excess of 11 deoxycortisterone in 17 hydroxylase deficiency, ACTH stimulation causes what two predominating symptoms to occur?

Answer 20

1. Ambiguous genetalia from lack of androgens
2. Hypertension d/t mineralcorticoid activity and increased corticosterone w/ glucocorticoid activity